Mycobacterium Tuberculosis Osteomyelitis from Cellular Bone Matrix Allograft: JBJS Case Connector Report

In this post, Dr. Thomas Bauer, Co-Editor of JBJS Case Connector, discusses a recent report of 2 cases of Mycobacterium tuberculosis osteomyelitis after spinal fusion resulting from contaminated cellular bone matrix.   

---

Bone allograft products have a long history of safety, thought in part to be due to a combination of donor screening, aseptic handling, and processing that has removed all viable donor cells. Enthusiasm for the concept of musculoskeletal progenitor cells has persisted, however, and some tissue allograft processors have developed bone allograft products that are processed in a way that is claimed to retain viable mesenchymal stromal cells.  

In a recent report in JBJS Case Connector, Issa and co-authors present the cases of 2 patients who had received a “cellular bone matrix” preparation (FiberCel; Aziyo Biologics) at an outside hospital while undergoing spinal fusion. Both patients were found to have developed Mycobacterium tuberculosis osteomyelitis and survived, but both required additional surgery as well as medical treatment. Of relevance to the diagnosis, acid-fast bacilli stains were positive in both patients, but multiple specimens submitted for next-generation sequencing (MicroGenDX) were negative. 

Cellular Bone Matrix Leading to Disseminated Tuberculosis After Spinal Fusion: A Report of 2 Cases 

The M. tuberculosis outbreak itself was first recognized when personnel in a Delaware acute care hospital reported 7 patients who developed tuberculosis (TB) after spinal surgery in the spring of 2021¹. The relevant lot of FiberCel was identified and recalled², but investigations subsequently determined that 113 patients had received TB-contaminated FiberCel allograft from a single donor. At least 3 of those patients died as a result of the infection, at least 83 recipients developed extrapulmonary tuberculosis at the surgical site, 27 developed pulmonary symptoms, and 48 underwent additional surgery. The donor was found to have been an 80-year-old man who had unrecognized risk factors, including frequent travel to an area endemic for TB. Apparently, a donor risk assessment interview had identified symptoms compatible with TB, but the donor had a history of a negative TB skin test, and his cough and recent weight loss were attributed to concurrent heart and renal failure^3,4.  

After death, the donor’s bones were manufactured into an allograft product that was reported to retain live cells. Bioburden testing for bacteria and fungi (but not M. tuberculosis) had been performed after harvest, but subsequent testing of unimplanted product from the contaminated lot suggests a high mycobacterial load in the allograft material³. 

In addition to the patients who received the contaminated bone allograft product, further investigation by the Centers for Disease Control and Prevention (CDC) identified 73 health-care personnel from the treating hospitals who developed latent TB infection after exposure in operating suites, sterile processing departments, post-anesthesia care units, or inpatient units⁴. Many exposures were from surgical sites, wounds, or activities related to contaminated procedural or surgical equipment, such as stirring graft matrix prior to implantation or irrigating infected wounds during revision surgeries. 

It has also been suggested that other components of the allograft, including live cells and bone morphogenetic proteins, might have contributed to mycobacterial growth³. 

In an editorial almost 7 years ago, JBJS reminded readers that viable cell products for musculoskeletal applications were required by the U.S. Food and Drug Administration to be minimally manipulated, to preserve the relevant characteristics relative to repair, to be intended for homologous use only, and not to be combined with another carrier. At the time of that editorial, efficacy was indeterminate, but few complications related to use of viable allograft cells in musculoskeletal applications had been reported.  

Based in part on the outbreak described above, the American Association of Tissue Banks has recommended that tissues obtained from donors with TB risk factors as well as tissues at highest risk for transmitting Mycobacteria (e.g., tissue with viable cells) be PCR tested for M. tuberculosis⁵.  

Aside from the above described incident, transmission of mycobacterial infections in bone graft seems to be rare, but there have been other cases of infections related to “stem cell therapy”⁶. As noted by Schwartz et al.³, it is appropriate for surgeons to consider the admittedly low risk of infection when using allograft preparations, especially those containing live cells, and that risk should be included in the informed consent process. 

Thomas W. Bauer, MD, PhD 

Co-Editor, JBJS Case Connector 

 

Cellular Bone Matrix Leading to Disseminated Tuberculosis After Spinal Fusion: A Report of 2 Cases 

---

References 

1. Li R, Wilson WW, Schwartz NG, Hernandez-Romieu AC, Glowicz J, Hanlin E, Taylor M, Pelkey H, Briody CA, Gireesh L, Eskander M, Lingenfelter K, Althomsons SP, Stewart RJ, Free R, Annambhotla P, Basavaraju SV, Wortham JM, Morris SB, Benowitz I, Haddad MB, Hong R, Drees M. Notes from the field: tuberculosis outbreak linked to a contaminated bone graft product used in spinal surgery—Delaware, March-June 2021. MMWR Morb Mortal Wkly Rep. 2021;70(36):1261-3.
2. Food and Drug Administration. Urgent voluntary notification: FiberCel Fiber Viable Bone Matrix (“FiberCel”)—lot number: NMDS210011. Silver Spring, MD: US Department of Health and Human Services, Food and Drug Administration; 2021. Accessed 2023 May 8. https://www.fda.gov/vaccines-blood-biologics/recalls-biologics/urgent-voluntary-notification-fibercel-fiber-viable-bone-matrix-fibercel-lot-number-nmds210011 
3. Schwartz NG, Hernandez-Romieu AC, Annambhotla P, Filardo TD, Althomsons SP, Free RJ, Li R, Wyatt Wilson W, Deutsch-Feldman M, Drees M, Hanlin E, White K, Lehman KA, Thacker TC, Brubaker SA, Clark B, Basavaraju SV, Benowitz I, Burton Glowicz J, Cowan LS, Starks AM, Bamrah Morris S, LoBue P, Stewart RJ, Wortham JM, Haddad MB. Nationwide tuberculosis outbreak in the USA linked to a bone graft product: an outbreak report. Lancet Infect Dis. 2022;22(11):1617-25. 
4. Ruoran Li, Molly Deutsch-Feldman, Tamasin Adams, Michelle Law, Chinpar Biak, Erika Pitcher, Marci Drees, Alfonso C Hernandez-Romieu, Thomas D Filardo, Tracina Cropper, Angelica Martinez, W Wyatt Wilson, Sandy P Althomsons, Sapna Bamrah Morris, Jonathan M Wortham, Isaac Benowitz , Noah G Schwartz, Kelly White, Maryam B Haddad, Janet B Glowicz; Bone Allograft Tuberculosis Investigators. Transmission of Mycobacterium tuberculosis to healthcare personnel resulting from contaminated bone graft material, United States, June 2021 – August 2022. Clinical Infect Dis. 2023 Jan 20;ciad029. Online ahead of print.
5. American Association of Tissue Banks. Bulletin 22–2: recommendation issued to tissue banks regarding the risk of Mtb transmission. March 22, 2022. Accessed 2023 May 8. https://www.aatb.org/bulletin-22-2
6. Hartnett KP, Powell KM, Rankin D, Gable P, Kim JJ, Spoto S, Breaker E, Hunter R, Dotson N, McAllister G, Stevens V, Halpin AL, Houston H, Epson E, Malarkey M, Mendoza M, McNeill L, Perkins KM. Investigation of bacterial infections among patients treated with umbilical cord blood-derived products marketed as stem cell therapies. JAMA Netw Open. 2021 Oct 1;4(10):e2128615. Published online 2021 Oct 7.